Field
Disclosed herein are methods and algorithms for calibrating an optical analyte sensor in vivo.
Description of the Related Art
Analyte sensors, such as glucose sensors, for detecting and measuring the presence of different chemical species in samples are well known. To assure analyte measurement accuracy, whether as a gauge of the amount of analyte present or to agree with a measurement made by another instrument, an analyte sensor generally requires calibration. Such calibration is frequently necessary to account for sensor-to-sensor variation and for differences in the environment where the sensor will be placed.
Current sensor calibration can be time-consuming, uncomfortable, and intrusive for a patient, requiring multiple blood draws or constant sampling for ex-vivo analysis of blood sugar concentration to compare to a signal comprising the output of the analyte sensor. In cases where the sensor output is not linear when compared to the concentration of analyte, or only linear for a range of concentrations, additional complexity and potential uncertainty arises, requiring greater attention, more time, and more difficulty in performing a reliable calibration.
In addition, analyte measurements of the same sample taken by different methodologies may result in different concentrations of analyte being reported. These differences in concentrations reported for the same sample may be due to differences in the analytical technique, differences in sample preparation, or for other reasons as well. For example, some analyte measurement techniques dilute a sample of blood prior to determining the analyte level in solution, while other techniques simply determine the analyte level on a non-diluted sample of blood. In some instances, such dilution can result in additional analyte being extracted from cells present in the blood sample, resulting in a change in the amount of analyte that would be reported by the different methods. Other changes in technique can also result in shifts in reported values, such as when samples are filtered or centrifuged as a part of the procedure, or when a sensor based on a different technology is used. In some instances, problems can occur when measurements for a patient are made by one methodology, and the treatment protocol had been determined based on another methodology.
Because of the above problems, calibration of some sensors has been performed outside of a patient's blood stream. While providing for less discomfort to a patient, calibration outside of a patient's body may not be as accurate as calibration inside a patient's blood stream, where the sensor could take into account the physiological conditions of the patient. Errors in calibration of analyte sensors can lead to erroneous measurements. Reliance on such erroneous measurements, such as for medical treatment, or a mismatch between analytical technique and treatment protocol can lead to adverse responses and possibly life-threatening situations. In view of the foregoing, there is a need for improved methods for calibration of analyte sensors in vivo while minimizing the inconveniences for the patient.